Development of 2A peptide-based strategies in the design of multicistronic vectors

被引:207
作者
Szymczak, AL [1 ]
Vignali, DAA [1 ]
机构
[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
关键词
2A peptide; gene therapy; IRES; vectors;
D O I
10.1517/14712598.5.5.627
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
As science progresses in its understanding of diseases and their treatment, advances have been made in the biotechnology used in disease therapy. Most gene therapy approaches utilise viral vectors to deliver genes of interest. However, multiple proteins are often involved in disease processes and there is often a need to efficiently deliver more than one gene. Researchers have employed several strategies to accomplish this goal. When designing vectors to express multiple genes, there are several factors that need to be taken into account, including cell type, the activity of the protein of interest and subcellular protein localisation. In most cases, it is ideal for each protein to be expressed at comparable levels, a leading issue with traditional strategies for multigene expression. This review describes some of the techniques that have been used to express multiple genes, and will focus on the use of 2A peptides or 2A peptide-like sequences in the design of multicistronic vectors that may alleviate some of these issues.
引用
收藏
页码:627 / 638
页数:12
相关论文
共 102 条
[1]   The majority of immunogenic epitopes generate CD4+ T cells that are dependent on MHC class II-bound peptide-flanking residues [J].
Arnold, PY ;
La Gruta, NL ;
Miller, T ;
Vignali, KM ;
Adams, PS ;
Woodland, DL ;
Vignali, DAA .
JOURNAL OF IMMUNOLOGY, 2002, 169 (02) :739-749
[2]   CIS-ACTING REGULATORY ELEMENTS WITHIN GAG GENES OF AVIAN RETROVIRUSES [J].
ARRIGO, S ;
YUN, M ;
BEEMON, K .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (01) :388-397
[3]   EXPRESSION OF COMPLETE CHICKEN THYMIDINE KINASE GENE INSERTED IN A RETROVIRUS VECTOR [J].
BANDYOPADHYAY, PK ;
TEMIN, HM .
MOLECULAR AND CELLULAR BIOLOGY, 1984, 4 (04) :749-754
[4]   AN INTERNAL RIBOSOMAL ENTRY SIGNAL IN THE RAT VL30 REGION OF THE HARVEY MURINE SARCOMA-VIRUS LEADER AND ITS USE IN DICISTRONIC RETROVIRAL VECTORS [J].
BERLIOZ, C ;
TORRENT, C ;
DARLIX, JL .
JOURNAL OF VIROLOGY, 1995, 69 (10) :6400-6407
[5]   TRANSCRIPTIONAL INTERACTION BETWEEN RETROVIRAL LONG TERMINAL REPEATS (LTRS) - MECHANISM OF 5' LTR SUPPRESSION AND 3' LTR PROMOTER ACTIVATION OF C-MYC IN AVIAN B-CELL LYMPHOMAS [J].
BOERKOEL, CF ;
KUNG, HJ .
JOURNAL OF VIROLOGY, 1992, 66 (08) :4814-4823
[6]   PICORNAVIRUS INTERNAL RIBOSOME ENTRY SEGMENTS - COMPARISON OF TRANSLATION EFFICIENCY AND THE REQUIREMENTS FOR OPTIMAL INTERNAL INITIATION OF TRANSLATION IN-VITRO [J].
BORMAN, AM ;
BAILLY, JL ;
GIRARD, M ;
KEAN, KM .
NUCLEIC ACIDS RESEARCH, 1995, 23 (18) :3656-3663
[7]   Comparison of picornaviral IRES-driven internal initiation of translation in cultured cells of different origins [J].
Borman, AM ;
LeMercier, P ;
Girard, M ;
Kean, KM .
NUCLEIC ACIDS RESEARCH, 1997, 25 (05) :925-932
[8]  
Bouayadi K, 1997, CANCER RES, V57, P110
[9]   Production of interleukin-12 as a self-processing 2A polypeptide [J].
Chaplin, PJ ;
Camon, EB ;
Villarreal-Ramos, B ;
Flint, M ;
Ryan, MD ;
Collins, RA .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1999, 19 (03) :235-241
[10]   A 9-nt segment of a cellular mRNA can function as an internal ribosome entry site (IRES) and when present in linked multiple copies greatly enhances IRES activity [J].
Chappell, SA ;
Edelman, GM ;
Mauro, VP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (04) :1536-1541